Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. The VANISH Randomized Clinical Trial

IMPORTANCE: Norepinephrine is currently recommended as the first-line vasopressor in septic shock; however, early vasopressin use has been proposed as an alternative. OBJECTIVE: To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: A factorial (2×2), double-blind, randomized clinical trial conducted in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015, enrolling adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock. INTERVENTIONS: Patients were randomly allocated to vasopressin (titrated up to 0.06 U/min) and hydrocortisone (n = 101), vasopressin and placebo (n = 104), norepinephrine and hydrocortisone (n = 101), or norepinephrine and placebo (n = 103). MAIN OUTCOMES AND MEASURES: The primary outcome was kidney failure-free days during the 28-day period after randomization, measured as (1) the proportion of patients who never developed kidney failure and (2) median number of days alive and free of kidney failure for patients who did not survive, who experienced kidney failure, or both. Rates of renal replacement therapy, mortality, and serious adverse events were secondary outcomes. RESULTS: A total of 409 patients (median age, 66 years; men, 58.2%) were included in the study, with a median time to study drug administration of 3.5 hours after diagnosis of shock. The number of survivors who never developed kidney failure was 94 of 165 patients (57.0%) in the vasopressin group and 93 of 157 patients (59.2%) in the norepinephrine group (difference, -2.3% [95% CI, -13.0% to 8.5%]). The median number of kidney failure-free days for patients who did not survive, who experienced kidney failure, or both was 9 days (interquartile range [IQR], 1 to -24) in the vasopressin group and 13 days (IQR, 1 to -25) in the norepinephrine group (difference, -4 days [95% CI, -11 to 5]). There was less use of renal replacement therapy in the vasopressin group than in the norepinephrine group (25.4% for vasopressin vs 35.3% for norepinephrine; difference, -9.9% [95% CI, -19.3% to -0.6%]). There was no significant difference in mortality rates between groups. In total, 22 of 205 patients (10.7%) had a serious adverse event in the vasopressin group vs 17 of 204 patients (8.3%) in the norepinephrine group (difference, 2.5% [95% CI, -3.3% to 8.2%]). CONCLUSIONS AND RELEVANCE: Among adults with septic shock, the early use of vasopressin compared with norepinephrine did not improve the number of kidney failure-free days. Although these findings do not support the use of vasopressin to replace norepinephrine as initial treatment in this situation, the confidence interval included a potential clinically important benefit for vasopressin, and larger trials may be warranted to assess this further. TRIAL REGISTRATION: clinicaltrials.gov Identifier: ISRCTN 20769191

Development of thermally stable phosphonitrile elastomers for advanced aerospace structures

Attempts to prepare low molecular weight, curable poly-(fluoroalkoxyphosphazenes) have been successful. Derivatization of /Cl2PN/n polymer with alkoxides gave functionally reactive terpolymers. These terpolymers could be crosslinked with polyisocyanates at room temperature. Attempts to control molecular weight have not been as successful. The effects of (Cl2PN)3 monomer purity, use of (Cl2PN)3,4 mixture, and early termination of the bulk polymerization of (Cl2PN)3 were studied briefly. Both low and high molecular weight polymers were obtained. Reaction of NH4Cl with PCl5 with subsequent heating to give chain extension gave either gels of oils with molecular weights of several thousand. The stabilization of poly-(fluoroalkoxyphosphazene) was investigated. The results generally were inconclusive, but acids were found to be deleterious while bases had little discernible effect. Improvements in stability by modification of end groups was inconclusive

Letter from Rose S. Taylor to John Muir, [1913 Apr].

(Apr. 1913)Mr. John Muir,Martinez, Calif.Permit me to say to you that the Story of my Boyhood and Youth has found a great place in our house and in our hearts.We gave it to our son Paul, who has entered the university. The book is full of inspiration and courage and the atmosphere05412 of the early Wisconsin days. We are Wisconsin people and are familiar with the scenes of the book. I\u27m glad you wrote this book. I\u27m prouder than ever of the U.W.Pardon me if this letter is an intrusion on your time.Very trulyRose W. TaylorU.W. \u2785Mrs. H. J. Taylor1711 Douglas St,Sioux City, I

Coal-rock interface detector

A coal-rock interface detector is presented which employs a radioactive source and radiation sensor. The source and sensor are separately and independently suspended and positioned against a mine surface of hydraulic pistons, which are biased from an air cushioned source of pressurized hydraulic fluid

How do you spell bird? Effective parent programs to enhance 4-6 year old children's literacy development

This research examined the effectiveness of parent programs designed for families to support the literacy learning of their 4-6 year old children. The project began with a literature review analysing six established, effective parent programs that have been reported in the international and national research literature. An analysis of what made each of the programs effective entailed an analysis of the program's target population, the project inputs and activities and the initial, immediate and long term outcomes. To explore further what local parents and families view as effective parent programs for 4-6 year old children the research explored individual site-specific parent programs in operation in South Australian childcare centres, preschools and schools in a range of diverse socioeconomic and geographic sites. Parents and teachers engaged in focus groups to describe ways the schools and centres sustain links between home and school learning. To assess the elements of two existing parent programs to support children's early literacy development, parents and teachers participated in several focus groups. The two programs were the parent component of The Abecedarian Program (2001, 1979) developed in the United States and the South Australian Early Childhood Literacy Includes Parents Staff and Education ECLIPSE program (1997) developed by the South Australian Department of Education and Children's Services (DECS)

Modulation of Immunological Pathways in Autistic and Neurotypical Lymphoblastoid Cell Lines by the Enteric Microbiome Metabolite Propionic Acid

Propionic acid (PPA) is a ubiquitous short-chain fatty acid which is a fermentation product of the enteric microbiome and present or added to many foods. While PPA has beneficial effects, it is also associated with human disorders, including autism spectrum disorders (ASDs). We previously demonstrated that PPA modulates mitochondrial dysfunction differentially in subsets of lymphoblastoid cell lines (LCLs) derived from patients with ASD. Specifically, PPA significantly increases mitochondrial function in LCLs that have mitochondrial dysfunction at baseline [individuals with autistic disorder with atypical mitochondrial function (AD-A) LCLs] as compared to ASD LCLs with normal mitochondrial function [individuals with autistic disorder with normal mitochondrial function (AD-N) LCLs] and control (CNT) LCLs. PPA at 1 mM was found to have a minimal effect on expression of immune genes in CNT and AD-N LCLs. However, as hypothesized, Panther analysis demonstrated that 1 mM PPA exposure at 24 or 48 h resulted in significant activation of the immune system genes in AD-A LCLs. When the effect of PPA on ASD LCLs were compared to the CNT LCLs, both ASD groups demonstrated immune pathway activation, although the AD-A LCLs demonstrate a wider activation of immune genes. Ingenuity Pathway Analysis identified several immune-related pathways as key Canonical Pathways that were differentially regulated, specifically human leukocyte antigen expression and immunoglobulin production genes were upregulated. These data demonstrate that the enteric microbiome metabolite PPA can evoke atypical immune activation in LCLs with an underlying abnormal metabolic state. As PPA, as well as enteric bacteria which produce PPA, have been implicated in a wide variety of diseases which have components of immune dysfunction, including ASD, diabetes, obesity, and inflammatory diseases, insight into this metabolic modulator may have wide applications for both health and disease

Internet-based early intervention to prevent poststraumatic stress disorder in injury patients: Randomized controlled trial.

Background: Posttraumatic stress disorder (PTSD) develops in 10-20% of injury patients. We developed a novel, self-guided Internet-based intervention (called Trauma TIPS) based on techniques from cognitive behavioral therapy (CBT) to prevent the onset of PTSD symptoms. Objective: To determine whether Trauma TIPS is effective in preventing the onset of PTSD symptoms in injury patients. Methods: Adult, level 1 trauma center patients were randomly assigned to receive the fully automated Trauma TIPS Internet intervention (n=151) or to receive no early intervention (n=149). Trauma TIPS consisted of psychoeducation, in vivo exposure, and stress management techniques. Both groups were free to use care as usual (nonprotocolized talks with hospital staff). PTSD symptom severity was assessed at 1, 3, 6, and 12 months post injury with a clinical interview (Clinician-Administered PTSD Scale) by blinded trained interviewers and self-report instrument (Impact of Event Scale-Revised). Secondary outcomes were acute anxiety and arousal (assessed online), self-reported depressive and anxiety symptoms (Hospital Anxiety and Depression Scale), and mental health care utilization. Intervention usage was documented. Results: The mean number of intervention logins was 1.7, SD 2.5, median 1, interquartile range (IQR) 1-2. Thirty-four patients in the intervention group did not log in (22.5%), 63 (41.7%) logged in once, and 54 (35.8%) logged in multiple times (mean 3.6, SD 3.5, median 3, IQR 2-4). On clinician-assessed and self-reported PTSD symptoms, both the intervention and control group showed a significant decrease over time (P<.001) without significant differences in trend. PTSD at 12 months was diagnosed in 4.7% of controls and 4.4% of intervention group patients. There were no group differences on anxiety or depressive symptoms over time. Post hoc analyses using latent growth mixture modeling showed a significant decrease in PTSD symptoms in a subgroup of patients with severe initial symptoms (n=20) (P<.001). Conclusions: Our results do not support the efficacy of the Trauma TIPS Internet-based early intervention in the prevention of PTSD symptoms for an unselected population of injury patients. Moreover, uptake was relatively low since one-fifth of individuals did not log in to the intervention. Future research should therefore focus on innovative strategies to increase intervention usage, for example, adding gameplay, embedding it in a blended care context, and targeting high-risk individuals who are more likely to benefit from the intervention